Emerging roles of PPR proteins in trypanosomes: switches, blocks, and triggers

Mitochondrial genomes of trypanosomes are composed of catenated maxicircles and mini-circles that are densely packed into a nucleoprotein structure called the kinetoplast. Maxicircle DNA (~25 kb long, 20-50 copies) resembles a typical mitochondrial genome bearing rRNA and respiratory complex subunits genes, and also contains 12 cryptogenes whose transcripts require U-insertion/deletion editing to assemble protein-coding sequences. Production of guide RNAs for the editing process remains the only established function of mini-circle DNA (~1 kb, ~10000 copies). Although editing remains the most studied step in mRNA biogenesis, recent investigations illuminated complex nucleolytic processing and pre- and post-editing 3' modification events that ultimately create translation-competent mRNAs. Key mRNA 3' processing enzymes, such as KPAP1 poly(A) polymerase and RET1 TUTase, have been identified but the mechanisms regulating their activities remain poorly understood. Discoveries of multiple pentatricopeptide repeat-containing (PPR) proteins populating polyadenylation complex and ribosomal subunits opened exciting experimental prospects that may ultimately lead to an integrated picture of mitochondrial gene expression.